Field of Invention
The present invention is directed to the field of biological analysis. In particular the field of the invention is directed to measuring biological activity at a cellular level.
Description of the Related Technology
The fundamental limitation of the currently available technology is that it requires many thousands of cells in the cell culture or tissue to produce sufficient signal of oxygen or glucose consumption, exchange of ions such as sodium and potassium, release of molecules such as lactic acid or other signals related to cell functionality. The resulting measurements provide information about cellular function averaged over a relatively large cell population. However, most cell populations have large heterogeneity of cellular behaviors and functions, even within genetically identical populations. Some cells being of a different phenotype may respond differently to external stimuli, for example, consuming oxygen at dramatically different rates than others. Such heterogeneity is an important property of many tissues and disease types.
The only known methodology for single cell function measurements such as respirometry is based on housing the cell being examined in a sealed micro-chamber. The main shortcomings of this scaled micro-chamber approach is that the relatively rapid depletion of essential molecules such as oxygen or nutrients as well as accumulation of carbon dioxide has the potential to change the observed cell behavior over time. Sealed chamber measurements must be carried out sufficiently quickly, usually faster than within few minutes, making it impossible to study cell behavior over longer time periods. Furthermore, sealed chamber approach to respirometry does not permit injection of molecules that can modify various aspects of cellular metabolism.